A Phase I/II, First-in-Human (FIH), Open-Label, Multiple Centre Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Efficacy of LM-350 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 4
- 主要终点
- Temperature (Celsius)
研究概览
简要总结
For Phase I Dose Escalation Stage, to assess the safety and tolerability of LM-350 in patients with advanced solid tumors,determine the maximum tolerated dose (MTD) or optimal biological dose (OBD), and explore the relationship between the biomarkers and the anti-tumor activity of LM-350.
For Phase II Dose Expansion Stage, to assess the preliminary anti-tumor activity of LM-350 in patients with advanced solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects who are willing to participate in the study and sign the informed consent form (ICF) prior to any procedure.
- •Participant must be ≥18 years or the legal age of consent at the time of signing the ICF.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Life expectancy ≥ 3 months.
- •Patients with advanced solid tumors confirmed by histopathological diagnosis who have failed standard treatment, are intolerant to standard treatment, or for whom standard treatment is currently unsuitable.
- •Pre-treatment archived tumour tissue (within 3 years) or on-treatment tumour biopsy could be provided for biomarker analysis.
- •Must have at least one measurable lesion according to RECIST v1.
- •Adequate organ and bone marrow function as defined by protocol.
- •Subjects who are able to communicate well with investigators and understand and adhere to the requirements of this study.
排除标准
- •Participate in any other clinical trial within 28 days prior to 1st dosing of LM-
- •Subjects who have received treatment with the same targeting.
- •History of ≥ Grade 3 late diarrhea during or after previous treatment with a topoisomerase inhibitor.
- •Subjects who have received the following anti-tumor treatments within the specified time periods prior to the first dosing of LM-
- •Any adverse event from prior anti-tumour therapy has not yet recovered to ≤ grade 1 of CTCAE v5.
- •Subjects with uncontrolled tumour-related pain.
- •Subjects with known central nervous system (CNS) or meningeal metastasis.
- •Subjects who have clinically uncontrollable third-space fluid accumulation.
- •Subjects who experienced grade 3 or higher hypersensitivity to the treatment that contains monoclonal antibody.
- •Subjects who take systemic corticosteroids (≥ 10 mg/day of prednisone or equivalents) or other systemic immunosuppressive medications within 2 weeks prior to the first dose of LM-
- •Has a history of (noninfectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
- •Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, and any autoimmune, or prior pneumonectomy.
- •Use of any live attenuated vaccines within 28 days prior to 1st dosing of LM-
- •Current unstable of full-dose oral or parenteral anticoagulants or thrombolytic agents for > 2 weeks prior to the first dose of LM-
- •Subjects with active or a documented history of chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease).
- •Subjects with complete or incomplete intestinal obstruction within 3 months prior to the first dose of the study drug , orpatients who are currently at the risk of intestinal perforation.
- •Subjects who received major surgery or interventional treatment within 28 days prior to 1st dosing of LM-
- •Subjects who have severe cardiovascular disease.
- •Subjects who have uncontrolled or severe illness.
- •Subjects who have a history of immunodeficiency disease.
- •HIV infection, active infection including tuberculosis, HBV and HCV infection.
- •Subjects who have other active malignancies which are likely to require the treatment.
- •Child-bearing potential female who have positive results in pregnancy test or are lactating.
- •Subjects who have psychiatric illness or disorders that may preclude study compliance.
- •Subject who is judged as not eligible to participate in this study by the investigator.
研究组 & 干预措施
Phase I Dose Escalation Part and Dose Confirmation Part
干预措施: LM-350 for injection (Drug)
结局指标
主要结局
Temperature (Celsius)
时间窗: 78 weeks
Phase I
Pulse in BPM(Beat per Minute)
时间窗: 78 weeks
Phase I
Blood Pressure in mmHg
时间窗: 78 weeks
Phase I
Weight in Kg
时间窗: 78 weeks
Phase I
Height in centimeter
时间窗: 78 weeks
Phase I
Blood Routine examination -> Complete Blood Count
时间窗: 78 weeks
Phase I
Urine Routine examination ->Urinalysis
时间窗: 78 weeks
Phase I
Incidence of serious adverse events (SAEs)
时间窗: 78 weeks
Phase I
Incidence of dose-limitingtoxicity (DLT)
时间窗: 78 weeks
Phase I
Incidence of Treatment-Emergent Adverse Events (AEs)
时间窗: 78 weeks
Phase I
Blood Biochemistry test -> Electrolytes and Metabolic Parameters
时间窗: 78 weeks
Phase I
Coagulation function test-For the detection of Prothrombin time (PT), Activated partial thromboplastin time (APTT), International normalized
时间窗: 78 weeks
Phase I
Thyroid function test-For the detection of Thyroid-stimulating hormone (TSH), free T3, free T4
时间窗: 78 weeks
Phase I
Pregnancy test
时间窗: 78 weeks
Phase I
Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage
时间窗: 78 weeks
Phase I
12-lead electrocardiogram (ECG) in HR
时间窗: 78 weeks
Phase I
12-lead electrocardiogram (ECG) in RR
时间窗: 78 weeks
Phase I
12-lead electrocardiogram (ECG) in QRS
时间窗: 78 weeks
Phase I
12-lead electrocardiogram (ECG) in QT
时间窗: 78 weeks
Phase I
12-lead electrocardiogram (ECG) in QTcF
时间窗: 78 weeks
Phase I
ECOG(Eastern Cooperative Oncology Group) score
时间窗: 78 weeks
Phase I
Objective Response Rate (ORR)
时间窗: 130 weeks
Phase II
次要结局
- Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax)(130 weeks)
- PK Parameter:Time of Maximum Observed Concentration (Tmax)(130 weeks)
- PK Parameter: Area Under the Concentration-time Curve(AUC)(130 weeks)
- PK Parameter: Steady State Maximum Concentration(Cmax,ss) PK Parameter: Steady State Maximum Concentration(Cmax,ss)(130 weeks)
- PK Parameter: Steady State Minimum Concentration(Cmin,ss)(130 weeks)
- PK Parameter: Systemic Clearance at Steady State (CLss)(130 weeks)
- PK Parameter: Accumulation Ratio (Rac)(130 weeks)
- PK Parameter: Elimination Half-life (t1/2)(130 weeks)
- PK Parameter: Volume of Distribution at Steady-State (Vss)(130 weeks)
- PK Parameter: Degree of Fluctuation (DF)(130 weeks)
- Immunogenicity testing->Anti-Drug Antibody test(130 weeks)
- Objective Response Rate (ORR)(130 weeks)
- Duration of Response (DOR) in Month(130 weeks)
- Disease control rate (DCR) in percentage(130 weeks)
- Progression-free survival (PFS) in Month(130 weeks)
- Changes of target lesions from baseline in Millimeter(130 weeks)
- Incidence of adverse events (AEs)(130 weeks)
- Incidence of serious adverse events (SAEs)(130 weeks)
- Temperature (Celsius)(130 weeks)
- Pulse in BPM(Beat per Minute)(130 weeks)
- Blood Pressure in mmHg(130 weeks)
- Weight in Kg(130 weeks)
- Height in centimeter(130 weeks)
- Blood Routine examination -> Complete Blood Count(130 weeks)
- Urine Routine examination ->Urinalysis(130 weeks)
- Blood Biochemistry test -> Electrolytes and Metabolic Parameters(130 weeks)
- Coagulation function test-For the detection of Prothrombin time (PT), Activated partial thromboplastin time (APTT), International normalized ratio (INR)(130 weeks)
- Pregnancy test(130 weeks)
- Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage(130 weeks)
- ECOG(Eastern Cooperative Oncology Group) score(130 weeks)
- 12-lead electrocardiogram (ECG) in HR(130 weeks)
- 12-lead electrocardiogram (ECG) in RR(130 weeks)
- 12-lead electrocardiogram (ECG) in PR(130 weeks)
- 12-lead electrocardiogram (ECG) in QRS(130 weeks)
- 12-lead electrocardiogram (ECG) in QT(130 weeks)
- 12-lead electrocardiogram (ECG) in QTcF(130 weeks)
- Biomarker test -> Tumor tissue biomarker test(130 weeks)
- Overall survival (OS) in Month(130 weeks)